a study of anti-pd-l1 checkpoint antibody (ly3300054) alone and in combination in participants with advanced refractory solid tumors

Conditions: Solid Tumor; Microsatellite Instability-High (MSI-H) Solid Tumors; Cutaneous Melanoma; Pancreatic Cancer; Breast Cancer (HR+HER2-)

Summary: the main purpose of this study is to evaluate the safety and tolerability of anti-programmed cell death ligand 1 (pd-l1) checkpoint antibody ly3300054 in participants with advanced refractory solid tumors.


Eligibility criteria:
inclusion criteria: * histologic or cytologic confirmation of advanced solid tumor. * for ly3300054 + abemaciclib only: no participants with liver metastases. participants must have normal aspartate aminotransferase (ast), alanine aminotransferase (alt), total bilirubin, direct bilirubin. * for ly3300054 + abemaciclib in hr+, her- breast cancer: * express at least 1 of the hormone receptors \[hr; estrogen receptor (er) or progesterone receptor (pr)\] by immunohistochemistry (ihc) to fulfill the requirement for hr+ disease on the primary tumor or metastatic lesion of the breast cancer. er and pr assays are considered positive if there is at least 1% positive tumor nuclei in their sample as defined in the relevant american society of clinical oncology (asco)/college of american pathologists (cap) or local guidelines. * to fulfill the requirement of her2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of her2 by either ihc or in-situ hybridization (ish) as defined in the relevant asco/cap or local guidelines. * most recent hr and her2 receptor testing should be used to determine eligibility. * have previously received prior treatment with at least 1 but no more than 3 chemotherapy regimens in the metastatic setting. * have ast, alt, ggt, and ap that are ≤2.5x upper limit of normal (uln) and normal bilirubin (total and direct) regardless of liver involvement. * for ly3300054 + merestinib in pancreatic cancer: * histologically or cytological confirmed diagnosis of metastatic or locally advanced, unresectable pancreatic adenocarcinoma (excluding other pancreatic malignancies for example, acinar cell carcinomas, adenosquamous carcinomas, and neuroendocrine islet cell neoplasms). * have had disease progression, be refractory or intolerant to no more than 2 prior systemic regimens. * for ly3300054 + ly3321367 in pd-1/pd-l1-naive, msi-h/mmr-deficient advanced solid tumors: * have histologically or cytologically confirmed diagnosis of advanced solid tumor and shown to be msi-h or mmr-deficient. * for ly3300054 + ly3321367 in pd-1/pd-l1- resistant/refractory, msi-h/mmr-deficient advanced solid tumors: * have histologically or cytologically confirmed diagnosis of advanced solid tumor and shown to be msi-h or mmr-deficient. * prior exposure to pd-1/pd-l1 agent regardless of response. * for phase 1b ly3300054 monotherapy or combination therapy, no prior treatment with a pd-1 or pd-l1 agent is allowed. * exception: the ly3321367 combination in participants with pd-1/pd-l1- resistant/refractory, msi-h, where prior exposure to pd-1/pd-l1 agent required. * for phase 1a ly3300054 monotherapy or combination therapy, previous immunotherapy is acceptable if the following criteria are met: * must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy. * must have completely recovered or recovered to baseline prior to screening from any prior adverse events (aes) occurring while receiving prior immunotherapy. * must not have experienced a grade ≥3 immune-related ae or an immune-related neurologic or ocular ae of any grade while receiving prior immunotherapy. * must not have required the use of additional immunosuppressive agents other than corticosteroids for the management of an ae, not have experienced recurrence of an ae if re-challenged, and not currently require maintenance doses of \>10 milligrams prednisone or equivalent per day. * have at least 1 measurable lesion assessable using standard techniques by response evaluation criteria in solid tumors (recist) v1.1. * have adequate organ function. * have a performance status of 0 or 1 on the eastern cooperative oncology group (ecog) scale. * have an estimated life expectancy of ≥12 weeks, in the judgment of the investigator. * have submitted a tumor tissue sample, as follows: * for participants entering the phase 1a dose escalation: have submitted, if available, the most recent archival tumor tissue sample. * for those participating only in phase 1b expansions: have submitted tumor tissue sample from a newly obtained core or excisional biopsy for a tumor lesion (preferred) or a recent biopsy taken with 3 months prior to study enrollment and following the participants most recent prior systemic treatment and be willing to undergo a biopsy procedure during the study treatment period for collection of additional tumor tissue sample. exclusion criteria: * have a serious concomitant systemic disorder including human immunodeficiency virus (hiv), active hepatitis b virus (hbv), active hepatitis c virus (hcv), active autoimmune disorder or disease requiring high dose of steroids. * have a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection or chronic diarrhea. * have evidence of interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity or active, noninfectious pneumonitis. * have an active infection requiring systemic therapy. * have moderate or severe cardiovascular disease. * have symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment. * have received a live vaccine within 30 days before the first dose of study treatment. * have a significant bleeding disorder or vasculitis or had a grade ≥3 bleeding episode within 12 weeks prior to enrollment.

Keywords: pdl1 pd-l1